A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases

A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases

Copyright © 2016 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 174(2017) vom: 04. Jan., Seite 24-31
1. Verfasser: Ueki, Masahiro (VerfasserIn)
Weitere Verfasser: Yamada, Masafumi, Ito, Kenta, Tozawa, Yusuke, Morino, Saeko, Horikoshi, Yuho, Takada, Hidetoshi, Abdrabou, Shimaa Said Mohamed Ali, Takezaki, Shunichiro, Kobayashi, Ichiro, Ariga, Tadashi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Case Reports Journal Article Research Support, Non-U.S. Gov't Autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD) Coiled-coil domain Dominant negative Multifocal osteomyelitis STAT1 STAT1 Transcription Factor STAT1 protein, human
Beschreibung
Zusammenfassung:Copyright © 2016 Elsevier Inc. All rights reserved.
Heterozygous dominant-negative mutations of STAT1 are responsible for autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD). So far, only 7 mutations have been previously described and are localized to 3 domains: the DNA-binding domain, the SH2 domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c.749G>C, p.G250A (G250A) in STAT1 as a genetic cause of AD-MSMD in a patient with mycobacterial multiple osteomyelitis. This de novo heterozygous mutation was shown to have a dominant-negative effect on the gamma-activated sequence (GAS) transcriptional activity following IFN-γ stimulation, which could be attributable to the abolished phosphorylation of STAT1 from the wild-type (WT) allele. The three-dimensional structure of STAT1 revealed the G250 residue was located distant from a cluster of residues affected by gain-of-function mutations responsible for chronic mucocutaneous candidiasis
Beschreibung:Date Completed 13.06.2017
Date Revised 06.02.2018
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2016.11.004